Our data indicate that progesterone treatment of female monkeys increases their susceptibility to vaginal infection with SIV. We synchronized the menstrual cycle of monkeys by progesterone treatments so that all monkeys at the outset of any vaginal inoculation experiment would be at the same stage of the cycle and under progesterone influence. Using this method in 2 experiments resulted in infection of 9/11 or 5/6 monkeys, respectively. In the progesterone phase of the cycle vaginal pH is higher and the vaginal epithelium is thinner, which may be conducive to successful mucosal infection. Last year we reported that 5 monkeys which had received no progesterone did not become infected after vaginal inoculation with the same SIV stock (SIV/B670 Rh II) that had previoiusly infected synchronized monkeys successfully. We inoculated again these 5 monkeys along with 4 naive monkeys with a different SIV stock (SIV/B670 Clone 12) that had a 10-fold higher titer invitro. Again, none of the monkeys became infected. We then vaginally inoculated the SIV/B670 Rh II stock into 2 monkeys and the SIV/B670 Clone 12 stock into 3 monkeys whose cycles had been synchronized by progesterone treatments. All of these became infected. In addition, using a new stock (SIV/B670 Rh 3) we vaginally inoculated 3 monkeys whose cycles had been synchronized, 4 monkeys whose cycles had not been synchronized but which had received progesterone treatments for 15 days, and 4 monkeys which had received no progesterone treatments. All became infected except 1 of 4 monkeys which had received no progesterone treatment. These results confirmed that cycle synchronization and progesterone treatment rendered monkeys more susceptible to vaginal infection with SIV, and demonstrated that just 15 days of progesterone treatment was sufficient to increase the susceptibility. FUNDING NIH-N01-AI-15119 NIH-N01-AI-65310 PUBLICATIONS None